During his tenure as a Clinical Associate Physician in the Clinical Research Center at the University of Iowa, Dr. Hayford's research will concern the formation of anti-insulin antibodies as a result of treatment of diabetics with exogenous insulin. The physiologic significance of these antibodies on insulin metabolism, on insulin pharmacology and insulin binding at cell membrane receptors is incompletely characterized. Anti-insulin antibodies may act as circulating insulin carrier proteins, thus establishing two fractions (unbound and antibody bound) of insulin within the extracellular fluid. Although unbound insulin is probably the biologically active fraction, the antibody bound fraction may also have biologic relevance. Specifically, it is hypothesized that anti-insulin antibody, by its ability to absorb and release insulin from the insulin-antibody complex, acts a large circulating insulin reservoir, dampens fluctuations in unbound insulin and alters insulin pharmacokinetics. The two proposed projects will test in vivo the applicability of this hypothesis. Project 1 will investigate the role of these anti-insulin antibodies on insulin pharmacology, assessing the partitioning of total insulin between the unbound and antibody bound fraction. Project II will investigate the patterns of insulin response established by an artificial pancreas during standardized dietary challenges. These data should provide experimental evidence in vivo of the role that anti-insulin antibodies play in insulin metabolism and insulin pharmacology. If the hypothesis is confirmed by experimental testing, these data should assist in understanding one of the variables that influences the diabetic's response to administered insulin. Ultimately, this knowledge should assist in the development of insulin treatment regimens to achieve more optimal care of insulin-dependent diabetic subjects.